公开(公告)号：US20080177041A1

公开(公告)日：2008-07-24

申请号：US12055454

申请日：2008-03-26

申请人： LANCE E. STEWARD ,  Todd M. Herrington ,  Kei Roger Aoki

发明人： LANCE E. STEWARD ,  Todd M. Herrington ,  Kei Roger Aoki

IPC分类号： C07K14/33

CPC分类号： C07K14/33 ,  A61K38/00 ,  Y10S530/825

摘要： Modified neurotoxin comprising neurotoxin including structural modification, wherein the structural modification alters the biological persistence, preferably the biological half-life, of the modified neurotoxin relative to an identical neurotoxin without the structural modification. The structural modification includes addition or deletion of a leucine-based motif or parts thereof. In one embodiment, methods of making the modified neurotoxin include using recombinant techniques. In another embodiment, methods of using the modified neurotoxin to treat biological disorders include treating autonomic disorders, neuromuscular disorders or pains.

公开(公告)号：US20110287517A1

公开(公告)日：2011-11-24

申请号：US13112844

申请日：2011-05-20

申请人： LANCE E. STEWARD ,  SANJIV GHANSHANI ,  ESTER FERNANDEZ-SALAS ,  MARCELLA A. GILMORE ,  JOSEPH FRANCIS ,  KEI ROGER AOKI

发明人： LANCE E. STEWARD ,  SANJIV GHANSHANI ,  ESTER FERNANDEZ-SALAS ,  MARCELLA A. GILMORE ,  JOSEPH FRANCIS ,  KEI ROGER AOKI

IPC分类号： C12N9/52

CPC分类号： C12N9/52 ,  A61K38/4893 ,  C07K14/33 ,  C12Y304/24069

摘要： The specification discloses Clostridial toxins or Clostridial toxin chimeras comprising an inactivation cleavage site, polynucleotide molecules encoding such toxins or chimeras, compositions comprising such toxins or chimeras, and method of producing such toxins or chimeras.

摘要翻译： 本说明书公开了包含灭活切割位点的梭菌毒素或梭菌毒素嵌合体，编码这种毒素或嵌合体的多核苷酸分子，包含这种毒素或嵌合体的组合物，以及产生此类毒素或嵌合体的方法。

公开(公告)号：US20110294742A1

公开(公告)日：2011-12-01

申请号：US13209969

申请日：2011-08-15

申请人： LANCE E. STEWARD ,  ESTER G. FERNANDEZ-SALAS ,  MARCELLA A. GILMORE ,  JOSEPH FRANCIS ,  SHENGWEN LI ,  KEI ROGER AOKI

发明人： LANCE E. STEWARD ,  ESTER G. FERNANDEZ-SALAS ,  MARCELLA A. GILMORE ,  JOSEPH FRANCIS ,  SHENGWEN LI ,  KEI ROGER AOKI

IPC分类号： A61K38/16 ,  A61P25/14 ,  A61P1/00 ,  A61P27/02 ,  A61P25/00 ,  A61P13/10 ,  A61P17/00 ,  A61P21/02 ,  A61P29/00

CPC分类号： C07K14/33 ,  C07K2319/33 ,  C07K2319/55

摘要： The specification discloses modified Clostridial toxins comprising a PAR ligand domain, a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and a Clostridial toxin binding domain; polynucleotide molecules encoding modified Clostridial toxins comprising a PAR ligand domain, a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and a Clostridial toxin binding domain; and method of producing modified Clostridial toxins comprising a PAR ligand domain, a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and a Clostridial toxin binding domain.

摘要翻译： 该说明书公开了修饰的梭菌毒素，其包含PAR配体结构域，梭菌毒素酶促结构域，梭菌毒素易位结构域和梭菌毒素结合结构域; 编码经修饰的梭菌毒素的多核苷酸分子，其包含PAR配体结构域，梭菌毒素酶促结构域，梭菌毒素易位结构域和梭菌毒素结合结构域; 以及产生包含PAR配体结构域，梭菌毒素酶促结构域，梭菌毒素易位结构域和梭菌毒素结合结构域的修饰梭菌毒素的方法。

公开(公告)号：US20110111483A1

公开(公告)日：2011-05-12

申请号：US12904983

申请日：2010-10-14

申请人： LANCE E. STEWARD ,  MARCELLA A. GILMORE ,  ESTER G. FERNANDEZ-SALAS ,  SHENGWEN LI ,  RONALD G. MILLER ,  KEI ROGER AOKI

发明人： LANCE E. STEWARD ,  MARCELLA A. GILMORE ,  ESTER G. FERNANDEZ-SALAS ,  SHENGWEN LI ,  RONALD G. MILLER ,  KEI ROGER AOKI

IPC分类号： C12N1/21 ,  C12N15/31 ,  C12N15/70

CPC分类号： C12N9/52 ,  C07K14/33

摘要： Nucleic acid molecules that comprise modified open reading frames providing increased expression of the encoded active BoNT/E in a heterologous cell, expression constructs and cells comprising such nucleic acid molecules and methods useful for expressing the encoding active BoNT/E from such nucleic acid molecules, expression constructs and cells.

摘要翻译： 包含修饰的开放阅读框的核酸分子提供编码的活性BoNT / E在异源细胞中的表达增加，表达构建体和包含此类核酸分子的细胞和用于从该核酸分子表达编码活性BoNT / E的方法， 表达构建体和细胞。

公开(公告)号：US20100055727A1

公开(公告)日：2010-03-04

申请号：US11608912

申请日：2006-12-11

申请人： LANCE E. STEWARD ,  Ester Fernandez-Salas ,  Kei Roger Aoki

发明人： LANCE E. STEWARD ,  Ester Fernandez-Salas ,  Kei Roger Aoki

IPC分类号： C12Q1/37

CPC分类号： G01N33/582

摘要： The present invention provides clostridial toxin substrates useful in assaying for the protease activity of any clostridial toxin, including botulinum toxins of all serotypes as well as tetanus toxins. A clostridial toxin substrate of the invention contains a donor fluorophore; an acceptor having an absorbance spectrum overlapping the emission spectrum of the donor fluorophore; and a clostridial toxin recognition sequence that includes a cleavage site, where the cleavage site intervenes between the donor fluorophore and the acceptor and where, under the appropriate conditions, resonance energy transfer is exhibited between the donor fluorophore and the acceptor.

摘要翻译： 本发明提供了可用于测定任何梭菌毒素（包括所有血清型的肉毒毒素）以及破伤风毒素的蛋白酶活性的梭菌毒素底物。 本发明的梭菌毒素底物含有供体荧光团; 具有与供体荧光团的发射光谱重叠的吸收光谱的受体; 和梭菌毒素识别序列，其包括切割位点，其中切割位点插入供体荧光团和受体之间，并且在适当条件下，在供体荧光团和受体之间显示共振能量转移。

公开(公告)号：US20090042231A1

公开(公告)日：2009-02-12

申请号：US12192798

申请日：2008-10-21

申请人： LANCE E. STEWARD ,  Ester Fernandez-Salas ,  Kei Roger Aoki

发明人： LANCE E. STEWARD ,  Ester Fernandez-Salas ,  Kei Roger Aoki

IPC分类号： C12Q1/37

CPC分类号： C12Q1/37 ,  C07K14/001 ,  C07K14/435 ,  G01N33/56911 ,  G01N2333/33

摘要： The present invention provides clostridial toxin substrates useful in assaying for the protease activity of any clostridial toxin, including botulinum toxins of all serotypes as well as tetanus toxins. A clostridial toxin substrate of the invention contains a donor fluorophore; an acceptor having an absorbance spectrum overlapping the emission spectrum of the donor fluorophore; and a clostridial toxin recognition sequence that includes a cleavage site, where the cleavage site intervenes between the donor fluorophore and the acceptor and where, under the appropriate conditions, resonance energy transfer is exhibited between the donor fluorophore and the acceptor.

摘要翻译： 本发明提供了可用于测定任何梭菌毒素（包括所有血清型的肉毒毒素）以及破伤风毒素的蛋白酶活性的梭菌毒素底物。 本发明的梭菌毒素底物含有供体荧光团; 具有与供体荧光团的发射光谱重叠的吸收光谱的受体; 和梭菌毒素识别序列，其包括切割位点，其中切割位点插入供体荧光团和受体之间，并且在适当条件下，在供体荧光团和受体之间显示共振能量转移。

公开(公告)号：US20120115205A1

公开(公告)日：2012-05-10

申请号：US12871486

申请日：2010-08-30

申请人： LANCE E. STEWARD ,  MELVIN S. OKA

发明人： LANCE E. STEWARD ,  MELVIN S. OKA

IPC分类号： C12N9/52 ,  C12N15/57

CPC分类号： C07K14/33

摘要： The specification discloses modified Clostridial toxins comprising a Clostridial toxin substrate cleavage site located within the di-chain loop region; polynucleotide molecules encoding such modified Clostridial toxins comprising a Clostridial toxin substrate cleavage site located in the di-chain loop region; and method of producing modified Clostridial toxins comprising Clostridial toxin substrate cleavage site located within the di-chain loop region.

摘要翻译： 该说明书公开了修饰的梭菌毒素，其包含位于二链环区内的梭菌毒素底物切割位点; 编码这种经修饰的梭菌毒素的多核苷酸分子，其包含位于二链环区域中的梭菌毒素底物切割位点; 以及产生修饰梭菌毒素的方法，其包含位于二链环区内的梭菌毒素底物切割位点。

公开(公告)号：US20110111479A1

公开(公告)日：2011-05-12

申请号：US12871585

申请日：2010-08-30

申请人： LANCE E. STEWARD ,  MELVIN S. OKA

发明人： LANCE E. STEWARD ,  MELVIN S. OKA

IPC分类号： C12N9/48 ,  C07H21/04

CPC分类号： C07K14/33

摘要： The specification discloses modified Clostridial toxins comprising a Clostridial toxin substrate cleavage site located within the di-chain loop region; polynucleotide molecules encoding such modified Clostridial toxins comprising a Clostridial toxin substrate cleavage site located in the di-chain loop region; and method of producing modified Clostridial toxins comprising Clostridial toxin substrate cleavage site located within the di-chain loop region.

摘要翻译： 该说明书公开了修饰的梭菌毒素，其包含位于二链环区内的梭菌毒素底物切割位点; 编码这种经修饰的梭菌毒素的多核苷酸分子，其包含位于二链环区域中的梭菌毒素底物切割位点; 以及产生修饰梭菌毒素的方法，其包含位于二链环区内的梭菌毒素底物切割位点。